Assignment of the 1H and 13C NMR spectra of 1-methyl-6-phenyl-1 α ,4 α ,4a α ,5 α ,8 β ,8a α -hexahydro- 1,4-methanonaphthalene-5,8-diol

The synthesis of the title compound, 5 , a tricyclic diol, is described. The 1H and 13C NMR spectra of 5 have been analyzed, and individual spectral resonance signals have been assigned to specific 1H and 13C nuclei, respectively, in this compound.


Scheme 1
The reaction of 3a with NaBH 4 -CeCl 3 8 resulted in highly stereoselective reduction of both ketone C=O groups, thereby affording a single tricyclic diol, i.e., 5, mp 100.5-101.5 °C.Subsequent irradiation of this diol resulted in facile intramolecular [2 + 2] photocyclization, thereby affording the corresponding cage diol, 6, mp 166-167 °C (Scheme 2).The structure of 6 previously has been established unequivocally via single crystal X-ray structural analysis.5d Armed with this pertinent structural information, a detailed NMR study of tricyclic diol 5 was undertaken in an effort to assign all individual resonance signals in its 1 H and 13 C NMR spectra.The results of this study are described below.

Results and Discussion
NMR spectral assignments were made by using 1 H-1 H spin-spin coupling constant data together with information derived (i) by application of nuclear magnetic double resonance (NMDR) experiments, (ii) from a DEPT experiment, 9 and (iii) from 2D COSY and long-range HETCOR 10 spectra of 5.There are three well-resolved vinyl proton resonances in the 1 H NMR spectrum of 5 (δ 5.97, 6.15, and 6.50; see Figure 1).Inspection of the COSY spectrum (Figure 2) reveals that the resonance at δ 5.97 correlates strongly with that at δ 6.15 [i.e., H(2), H(3)], thereby permitting the remaining resonance signal at δ 6.50 to be assigned to H (7). Inspection of the HETCOR spectrum of 5 reveals that H(7) correlates with the 13 C resonance at δ 131.3, which thus can be assigned to C (7).The results of a DEPT experiment 9 permit assignment of the peaks at δ 52.3 (s), 59.5 (t), and 17.7 (q) to C(1), C(9), and the C(1)-CH 3 methyl carbon atoms, respectively.The methyl group protons appear as a singlet at δ 1.34, and the bridging methylene protons, H(9a) and H(9s) appear as an unresolved multiplet centered at δ 1.41 in the 1 H NMR spectrum of 5. Double irradiation of the proton signal at δ 2.81 [H(4)] causes the signal that corresponds to H(9a) and H(9s) to collapse to an AB pattern [δ A 1.39; δ B 1.42; J AB = 7.9 H).We are not able to further assign these two resonance signals, i.e., δ A and δ B , to individual protons H(9a) and H(9s) with certainty.
In addition, inspection of the long-range HETCOR spectrum reveals the existence of threebond correlations between the 13 C NMR resonance at δ 133.4 [C(3)] and the proton signals at δ 1.41 [H(9a), H(9s)] and 2.66, respectively.Thus, the resonance signal at δ 2.66 can be assigned to H(4a).Inspection of the HETCOR spectrum also permits assignment of the 13 C resonance signals at δ 49.1 and 50.3, which correlate with H(4a) and H(8a), respectively.
Only one vinyl carbon [C (6)] and the aromatic carbon resonances remain to be assigned.Data contained in the long-range HETCOR spectrum permits these assignments to be made with confidence.Thus, two long-range 1 H-13 C correlations appear, both of which involve the 13 C resonance signal at δ 148.9.One of these is a 3 J CH coupling to the proton resonance signal at δ 4.45 [H(8)], and the other is a 2 J CH correlation with the proton signal at δ 4.65 [H (5)].Hence, the 13 C resonance signal at δ 148.9 is assigned to C (6).
The lone remaining downfield singlet in the proton noise-decoupled 13 C NMR spectrum of 5 (at δ 140.0) therefore corresponds to the ipso aromatic carbon atom.Other aromatic carbon resonance signals appear as doublets at δ 125.6, 127.6, and 128.4.
Finally, the broad singlet at δ 2.97 in the 1 H NMR spectrum of 5 is assigned to the proton signals associated with the OH groups.This assignment is supported by the fact that this peak disappears from the spectrum upon addition of a few drops of D 2 O to the NMR sample tube that contains a CDCl 3 solution of 5.
The same computational approach was applied to the isomer of 5 in which the configurations of both C(5) and C(8) were inverted.For this cis diol (with exo-OH groups), the torsion angles along bonding pathways H(4a)-C(4a)-C(5)-H( 5) and H(8a)-C(8a)-C( 8)-H(8) were calculated (PCMODEL) to be 171° and -166°, respectively, with associated coupling constants of 10.23 and 9.75 Hz, respectively.Clearly, these calculations support the NMR coupling constant data upon which the suggested stereochemistries of the C(5)-OH and C(8)-OH bonds in 5 are based and also the conclusions derived from X-ray data for 6. 5d

Summary and Conclusions
Proton and 13 C NMR spectra of 5 have been assigned by using 1 H-1 H and 1 H-13 C coupling constant data together with information derived (i) by application of nuclear magnetic double resonance (NMDR) experiments, (ii) from data obtained by using a DEPT 9 experiment, and (iii) from relevant 2D COSY and long-range HETCOR 10 spectra.These spectral assignments are summarized in Table 1.Conclusions regarding the stereochemistry of the C(5)-OH and C(8)-OH bonds in 5 are supported by the results of molecular mechanics calculations.

Experimental Section
General Procedures.Melting points are uncorrected.Elemental microanalyses were performed by personnel at Galbraith Laboratories, Inc., Knoxville, TN.
1-Methyl-6-phenyl-1α,4α,4aα,8aα-tetrahydro-1,4-methanonaphthalene-5,8-dione (3a).A solution of 2-phenyl-p-benzoquinone (2, 5.0 g, 27 mmol) in benzene (60 mL) was cooled to 0-5 ºC via application of an external ice-water bath.To this cooled solution was added with stirring freshly cracked methylcyclopentadiene dimer 7 (2.18 g, 27 mmol).The resulting mixture was stirred at 0-5 °C during 4 h and then was concentrated in vacuo.The crude product, a mixture of [4 + 2] cycloadducts, was obtained as a yellow oil (6.47 g, 90%).This material was purified via flash column chromatography on silica gel by eluting with 5% EtOAc-hexane.A solution of 3a (1.85 g, 7.00 mmol) and CeCl 3 •7H 2 O (50 mL of a 0.60 M solution in MeOH, 30 mmol) was placed in a 250 mL round-bottom flask, which then was cooled to 0-5 °C via application of an external ice-water bath.To this cooled solution was added portionwise with stirring powdered NaBH 4 (570 mg, 28 mmol) in such a manner that the temperature of the reaction mixture did not exceed 5 °C.After the addition of NaBH 4 had been completed, the external ice-water bath was removed, and the stirred reaction mixture was allowed to warm gradually to ambient temperature during 0.5 h.Thin layer chromatographic (tlc) analysis of the reaction mixture indicated the absence of starting material (3a).The reaction was quenched via careful, portionwise addition of distilled water (50 mL).The resulting aqueous suspension was extracted with CH 2 Cl 2 (5 × 40 mL), dried (MgSO 4 ) and filtered, and the filtrate was concentrated in vacuo.Crude 5 thereby obtained was further purified via flash column chromatography on silica gel by eluting with 1:12 EtOAc-hexane.Fractional recrystallization of the eluate from EtOAc-hexane afforded pure 5 (1.5 g, 80%) as a colorless microcrystalline solid: mp 100.5-101.5 °C; IR (KBr) 3235 (s), 2930 (s), 1455 (m), 1360 (m), 1300 (m), 1170 (m), 1140 (m), 1030 (s), 950 (m), 780 (s), 720 cm -1 (s); 1 H NMR (CDCl 3 ) and 13  Acquisition of NMR spectral data.Proton and 13 C NMR spectra were recorded on Varian XL-300 and Varian VXR-300 NMR spectrometers by using 10% solutions in CDCl 3 with Me 4 Si internal standard.All 1D and 2D NMR pulse sequences were run by using standard software supplied by Varian Associates, Inc., version 6.1d.COSY spectra were obtained with spectral windows of 2186.3Hz in both dimensions, acquisition times of 0.23 s, 256 increments with 16 transients per increment, a delay of 2.0 s between transients, and data processed as 1024 X 1024 matrices.HETCOR and long-range HETCOR spectra were obtained by using acquisition times of 0.1 s, 256 increments with 64 transients per increment, a delay of 3.0 s between transients, and data processed as 2048 X 512 matrices.Long-range HETCOR experiments, performed by using a value of 8 Hz for the average long-range J CH , resulted in the acquisition of cross-peaks that correspond almost exclusively to three-bond correlations, 3 J CH .

Table 1 .
Proton and carbon chemical shifts and coupling constants in 5